Regulations

GUIDELINE FOR THE MANAGEMENT OF PATIENTS WITH IMMUNE MEDIATED HAEMOLYTIC ANAEMIA

Author: Dr L.L. van der Merwe

With Input from Prof A. Leisewitz, Dr A. Goddard, and Dr F. Kettner

All of the Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, Onderstepoort.

This article will primarily revolve around the management of dogs with immune mediated destruction of erythrocytes secondary to babesiosis and will discuss the ideal monitoring parameters for such a case. The other causes of secondary immune mediated haemolytic anaemia (IMHA) (drugs, bacterial infections, neoplasia, etc) or primary IMHA will not be discussed in any detail. They all show very similar presenting clinical sign, the disease will progress in a similar manner, and also develop similar complications although the long term prognosis does vary.

Immune mediated haemolytic anaemia secondary to babesiosis will be self evident due to the temporal relationship with finding the parasite on a stained bloodsmear, or a history of the patient having recently being treated for babesiosis. Other secondary causes of IMHA may be much more insidious and present a greater diagnostic challenge.

A.

The management and monitoring of a patient with haemolytic disease is a combination of both clinical and laboratory parameters.

1. Initial Patient Evaluation

Clinical signs are attributable to:

The degree of anaemia

Clinical signs attributable to anaemia will depend on the acuteness of the erythrocyte destruction and whether compensatory mechanisms have been activated.

The type of anaemia /haemolysis

Intravascular haemolysis

Hallmarks of this form of haemolysis include haemoglobinuria, haemoglobinaemia (red serum) and splenomegaly.

Extravascular haemolysis

Haemoglobinaemia and haemoglobinuria are absent as the erythrocytes aer lysed within phagocytes, but splenomegally is usually present.

Multi-systemic signs

Multi-systemic organ disease and/or failure may develop due to excessive or imbalanced cytokine secretion, the generation of free oxygen radicals, immune system dysregulation, endothelial damage, activation of the coagulation cascade, and disturbances in oxygen supply to the tissues. These complications may occur in any haemolytic disease be it babesiosis or primary IMHA.

2. Laboratory Evaluation

Full Evaluation of a blood smear

There is more to the evaluation of a blood smear than simply finding Babesia parasites:

Blood smears should always be good quality (with straight edges and well defined shoulders and a feather edge) and be properly stained for evaluation. Diagnosis may easily be missed if the quality of the smear is poor!

Red cell regenerative capacity should be assessed. Reticulocytes and normoblasts cause anisocytosis and polychromasia with an increase in red cell distribution width (RDW). The smear may appear non-regenerative in acute severe haemolysis as the bone marrow storage pool is used and a 2-3 day lag phase exists between red cell destruction and the appearance of a bone marrow response in the peripheral circulation. Acute babesiosis also seems to suppress the red cell regenerative capacity and the degree of regeneration in the presence of an active parasitaemia is usually inappropriate. Strong red cell regenerative responses should, however, be seen soon after elimination of the Babesia parasite.

Evaluate for concurrent Ehrlichia infectionin both the monocytes as well as the neutrophils. It is important to note that phagocytosed erythrocytes and parasites may resemble Ehrlichia morulae.

The presence of spherocytosis (small, dark staining, round erythrocytes without central pallor) indicates an immune-mediated process in red cell destruction. When more than 40-60% of red cells are spherocytes, a diagnosis of IMHA is strongly supported (although IMHA can be present with lower percentages).

Haemolytic disease, with or without a concurrent Babesia infection is an inflammatory process. Any inflammatory process in the body may induce a neutrophila with a left shift (increased band cells). This is usually a regenerative left shift and the presence thereof does not imply bacterial infection. Babesia infection without an inflammatory leukogram may be indicative of concurrent immunosuppressive disease (such as Ehrlichia, or distemper).

Packed cell volume (PCV):

The PCV is a percentage value obtained by centrifuging a blood sample in a micro-pipette tube. The haematocrit, on the other hand, is a haematology analyser calculated value based on red cell number and mean red cell volume.

Determine the initial PCV at time of presentation. Whether a blood transfusion is necessary is usually not a decision based on PCV alone. Other factors such as the clinical state of the dog, the availability of blood, the chronicity of the condition, ISA positivity with ongoing erythrocyte destruction, and financial constraints will all affect this choice. The initial PCV value is also useful to assist with the evaluation of response to therapy. Dogs that have chronic disease where the anaemia evolved slowly will be better able to cope with a low PCV than dogs that have experienced a rapid decrease in the PCV.

The buffy-coat can also be smeared to evaluate the white blood cells for the presence of Ehrlichia.

Together with the PCV the serum component should also be assessed.

If the sample is collected atraumatically, any red discolouration of the serum can be interpreted as intravascular haemolysis.

Total serum proteins (TSP) can be read by a refractometer. In young animals especially, verminosis is commonly occurs concurrently with babesiosis. A low TSP is an indication for a whole blood rather than a packed red cell transfusion, or for patient support with intravenous colloids administration.

Mild to moderate hypoalbuminaemia is common in babesiosis because of the inflammatory nature of the disease and the loss of albumin through damaged endothelium. However, the estimation of the TSP by a refractometer is a crude estimation of the albumin levels as increases in globulins (common in Babesia infection) may mask the decrease in albumin.

c) In-Saline Agglutination (ISA)/ Autoagglutination:

Auto-agglutination is the result of the spontaneous aggregation of erythrocytes due to the presence of erythrocyte-membrane bound immunoglobulins. These antibodies may be primary or acquired auto-antibodies. Autoagglutination must be differentiated from rouleaux formation, which occurs when erythrocytes stack together due to electrostatic forces caused by the presence of serum proteins (fibrinogen and acute phase globulins).

The ISA test is performed to check for an immune mediated reaction against the erythrocytes. Rouleaux will be dispersed by the addition of saline. False positives occur if insufficient saline is used to dilute the sample. The standard test procedure involves adding 1 drop of whole anti-coagulated blood to 6 drops of saline. This mixture should be well mixed. The slide must be evaluated under a microscope at 400 ´ magnification (no oil immersion) with low light intensity and the light condenser dropped low.

A negative ISA test does not, however, imply that IMHA is absent as the test is relatively crude. The interpretation can be graded according to the size of the aggregates.

It should be noted that the ISA test is useful and should be done in all cases of babesiosis at initial presentation together with the PCV. If it is not done at initial presentation, it is imperative that it be performed in all cases that respond poorly to therapy.

It should also be noted that response to immunosuppressive treatment for IMHA should be based on a rise in PCV and not by the resolution of a positive ISA reaction. Most dogs that respond well to immunosuppression (as seen by a rising PCV) will remain ISA positive for a few days despite good recovery. This occurs because the antibodies responsible for agglutination have a long half-life and will need to be cleared from circulation before the positive ISA reaction resolves. Therefore treat the PCV and not the ISA reaction.

d) Coombs’ Test

Although a threshold density of erythrocyte membrane bound antibodies is required to cause auto-agglutination, the sensitized reticuloendothelial system of the body can recognize cells that are marked (opsonised) with only very few antibodies.

The Coombs’ test is more sensitive than ISA in the diagnosis of IMHA as it involves the incubation of washed patient erythrocytes with serum containing anti-immunoglobulin antibodies which increases cross-linkages and thus potentiating agglutination at lower immunoglobulin levels. This test is indicated in patients exhibiting clinical and laboratory signs of regenerative anaemia with or without spherocytosis that do not show any evidence of blood loss. There is no need to perform this test if the patient is ISA positive.

As both the Coombs’ and ISA tests are affected by foreign erythrocytes, they must be performed PRIOR to any blood transfusion.

The initial evaluation of a patient with a haemolytic disease and laboratory monitoring is a synthesis of the abovementioned simple laboratory tests, a good clinical examination and common sense.

Always remember that TRENDS are all important and one-off examinations are often misleading.

3. Patient Monitoring

The complications associated with the haemolytic disease, be it babesiosis or primary or secondary IMHA, are generally due to a combination of anaemia and the systemic inflammatory reaction. The organs that are most frequently secondarily affected include the lungs (causing acute respiratory distress syndrome - ARDS), kidneys (causing acute renal failure - ARF), liver (causing icterus), erythrocytes (causing secondary IMHA), the brain (causing cerebral signs) and coagulation disorders (including pulmonary thromboembolism - PTE).

The assessment and monitoring must therefore include criteria that would evaluate these organ systems:

Lungs:

Monitor for sudden increases in respiratory rate and depth, referred breath sounds and increased effort of respiration. Always remember that very anaemic Babesia infected dogs always have profound blood gas and acid-base disturbances, which should resolve with blood transfusion. If respiratory signs worsen or improve only to suddenly deteriorate again following transfusion, consider ARDS or pulmonary thromboembolism. Increases in rate and depth are signs on an early decrease in pulmonary compliance due to fluid accumulation in the interstitium. By the time rales are auscultated the fluid accumulation is severe the alveoli are flooded, which may be a very poor prognostic sign. Radiographs, although helpful in confirming pathology do not take the place of a careful clinical evaluation as clinical changes will precede radiographic changes.

The initial monitoring plan of a sick Babesia patient should include frequent (hourly) assessment of the respiratory rate for at least the first 6 hours. This parameter is a simple yet sensitive indicator of decreased pulmonary function.

Kidneys:

Monitor for urine production, especially in haemoconcentrated babesiosis cases which very frequently present with ARF. Oliguria or anuria will precede the development of azotaemia (increases in urea and creatinine). Note that haemolysis will cause an increase in urea without a linear increase in creatinine. As such urea used alone is a poor indicator of renal function in this scenario and should always be used with creatinine or creatinine should be used alone.

Secondary/acquired IMHA:

The majority of clinically ill babesiosis infected dogs are Coombs’ positive and it is estimated that about 20% of cases seen at Outpatients section of the Onderstepoort Veterinary Academic Hospital are ISA positive at the time of Babesia diagnosis. The decision on how to proceed with these cases is based on the PCV at the time of diagnosis, ISA positivity, the colour of the serum, and the general clinical condition of the animal Many of these patients are ISA negative within 24 – 48 hours and thus do not require a long tapering course of prednisilone as eradication of the parasite has removed the trigger or the initial test was a false positive.

Occasionally a case can develop into a severe and clinically important secondary IMHA where auto-antibodies have developed against normal erythrocyte membrane antigens. These patients are challenging to manage and require aggressive therapy often with multiple transfusions and strong immunosuppressive therapy of several months duration.

Follow-up evaluation

It is important to request a re-evaluation of the dog the day following initial therapy. Uncomplicated cases will show a distinct improvement in habitus and clinical signs, although the PCV may still be quite low or even the same as the previous day. The parasitized cells are removed from circulation and the PCV may fall between 1-7% six hours after injecting of the babesiacidal agent. This percentage will obviously be affected by the regenerative capacity of the patient and the initial parasite density.

The monitoring of a patient with haemolytic disease /true IMHA involves the following basic in-house laboratory tests:

A repeat blood smear evaluation is essential to evaluate for regeneration and spherocytosis.

Ensure that the ISA test has been performed accurately.ISA must be evaluated microscopically. If the patient is positive at a 1:6 dilution with saline, increase the ration to a 1:20. A true ISA will still be positive whereas strong rouleaux will become negative.

Determine if the PCV is stable, decreasing or increasing. This parameter must be interpreted together with the identification of regeneration on the blood smear. IMHA cases are usually highly regenerative. Good regeneration with a stable PCV indicates ongoing erythrocyte destruction. Concomitant disease or chronic inflammation may decrease the regenerative capacity.

Evaluate serum colour for haemolysis

A typical regimen for a mild, babesiosis induced IMHA is a tapering dose of 2mg/kg decreasing to 0.5 mg/kg over 7 days.

B. Primary IMHA

The diagnosis of primary IMHA is challenging as it requires the exclusion of all possible secondary causes, which are numerous.

Drugs: - many medications are capable inducing IMHA. Vaccinations, especially rabies are probable causes if given less than 3-4 weeks previously. Potentiated sulpha drugs are major inducers of auto-immune reactions and may cause immune mediated thrombocytopaenia, IMHA, immune mediated polyarthritis and keratoconjunctivitis sicca (KCS). Cephalosporins and penicillins are also predisposed.

Neoplastic : Neoplastic cells may express non self antigens on their cell surfaces and as such may induce a variety on immune mediated conditions e.g. Thymoma induced Myaesthenia gravis.

A thorough, logical and often costly clinical and diagnostic plan is required to eliminate secondary causes.

Primary IMHA is more resistant to therapy and will require very gradual tapering with duration of therapy up to 6 months. In large breed dogs it is often advisable to add azathioprine early in the course of therapy to allow a reduction in the prednisilone dosage and thus decrease the side effects.

These dosage regimens are not a hard and fast rule but will be modified according to regular patient and haematology re-evaluations. These parameters should be re-assessed after each dosage reduction of the immunosuppressive therapy and at regular 2-3 week intervals to ensure that the condition is resolving. Often the prednisilone is tapered too rapidly and the haemolysis starts up again. If no monitoring is performed the animal will only present when the PCV is so low that it is once again causing clinical signs.

TABLE OF DRUGS WHICH CAN BE USED TO MANAGE IMHA ( summarized)

Drug

Mechanism

Regimen

Side effects/ comments

Prednisilone

* Blocks macrophages

* Decreases antibody production

* 4-5 days to effect

2-4 mg.kg/ d is immunosuppressive

(> 20kg = 3mg/day, <20kg = 4mg/kg/d … BSA effect)

taper initially by decr. dose by 50% every 2-3 weeks until 1mg/kg/day.

Maintain for 4 weeks, then decrease to 0.5mg/kgoid for 4w then 0,5mg/kg alt days for 4-8 weeks.

A patient that presents in shock or one that is unable to adequately compensate physiologically during an intervention such as anaesthesia. Shock can be defined and suspected under the following circumstances:

A dog or cat that is weak or collapsed. A depressed level of consciousness or sudden decrease in mentation are indicators of decompensation. These changes should be viewed in light of the nature of the trauma the patient has experienced (for example head trauma), or the possibility of a toxicity. Patients that have a sudden change in consciousness should be re-evaluated;

Shock typically causes a low rectal temperature (although temperature may be high in cases of sepsis or blood stream infections) and cold peripheral extremities;

Shock is associated with a tachycardia (although cats may have normal pulse and be in shock) or bradycardic; Tachycardia may be the result of pain in trauma patients and if the heart rate fails to decrease after an appropriate dose of an analgesic, hypovolaemia should be suspected. Patients that are tachycardic or normocardic where there is a suspicion of hypovolaemia or shock should be challenged with a fluid bolus equal to about 10% of their blood volume (approximately 10 ml/kg in dogs) given over 5-15 minutes. Changes in heart rate and blood pressure (the quality of the pulse) should be assessed. Before treating a patient that is bradycardic with atropine the following contraindications should be excluded: hypoxia, hypothermia and electrolyte imbalances (increased blood K+).

Capillary refill time is typically prolonged in established shock but in hyperdynamic shock and early septic shock this may not be the case (mucous membranes are also usually pale but may be injected in hyperdynamic or septic shock);

An attempt to feel the quality of the femoral or other peripheral arterial pulse should be made. If a peripheral pulse cannot be felt, arterial blood pressure is below 60 mmHg and this requires urgent attention.

Respiratory rate and pattern can be good indicator of patient stability. A fast respiratory rate with shallow breathing and an irregular pattern are indicators of an unstable patient. Rapid deep breathing cannot be sustained over a prolonged period and should warn about possible respiratory muscle failure.

Urine production is the ‘poor-man’s’ blood pressure machine. Measuring urine production is cheap and easy, requiring minimal invasiveness and time. It provides an objective means of evaluating blood pressure over time, rather than an instantaneous assessment at the time of the examination. Production in excess of 0.5ml/kg/hour usually indicates normal blood pressure

Blood glucose is often abnormal in unstable patients. It may both be high (as in some cases of septic shock and head trauma) and low (e.g. canine babesiosis)

Patients in compensated shock are more problematic as they may suddenly decompensate or may become unstable following the administration of anaesthesia.

A patient that has lost a large quantity of blood and is anaemic may be unable to maintain oxygen delivery under anaesthesia. Patients with long bone fractures can loose significant quantities of blood into the haematoma surrounding the fracture. Haematocrit is a poor indicator of acute blood loss. In these cases cardiovascular signs maybe a better indicator of the need for blood pressure support.

Patients showing severe dyspnoea should be regarded as unstable even if not in shock.

What does it mean to ‘stabilise’ a patient (what are the therapeutic end-points?)?

Stabilisation is the treatment that is given in the interim period from admission until the primary problem can be, or is, addressed. The benefit of stabilisation should always be greater than the cost of delaying primary treatment.

To restore arterial blood pressure and tissue oxygenation to as close to normal as possible. Blood pressure and tissue oxygenation cannot be directly assessed in most general practice environments in South Africa so we are forced to use markers of these indices. These have been listed above in question 1.

These markers should be showing a consistent tendency towards normalisation. It is important to appreciate that trends in the observations are very important and the establishment of trends requires frequent monitoring during the post event period. In critically ill animals it is probably unrealistic to expect a complete normalisation of these measurements and observations. This is a very important point to remember. There is no way that leaving a shocked patient in a cage overnight on a drip only to be re-examined the next morning for the first time can be seen as ethical practice.

What are the general therapeutic interventions used in stabilising a patient before any anaesthetic can be administered?

Caution in fluid administration must be exercised in patients with brain trauma, anuric renal failure, hypoproteinemia, lung oedema and lung contusions as fluid overload may be more rapidly lethal in these cases. Fluid overloading is more rapidly a problem in cats and more caution must be exercised when fluid loading this species.

The correction of any abnormal life-threatening biochemical disorders (such as severe hypoprotienaemia, hyperkalaemia, hypoglycaemia, hyper or hypoclacaemia or ketoacidosis), the correction of anaemia due to haemolysis (to a haematocrit of at least 20%) or whole blood loss (until blood pressure is above 70 mmHg – the approximate level at which femoral pulses can be palpated).

Ensure adequate urine production.

The correction of any life threatening respiratory abnormality such as serious thoracic effusion or flail chest. This should be accompanied by the administration of nasal oxygen.

The needle drainage of acute pericardial effusion that threatens cardiac output to the point of causing cardiogenic shock.

The correction (or at least an attempt to) of life threatening cardiac arrhythmias.

The arrest of any significant bleeding that can be stopped without surgical intervention.

The correction of acute bleeding tendencies due to clotting factor or platelet deficiencies to the point that spontaneous haemorrhage has subsided.

The supplementation of oxygen initially has few contraindications and can be safely used in most patients. Ventilation should be assessed for adequacy in terms of respiratory rate and tidal volume. Patients with slow respiratory rates (< 8 – 10) and low tidal volume should be ventilated to maintain adequate oxygenation with 100% oxygen until a diagnosis is made. Emergencies where ventilation is a consideration are usually caused by diseases of the neuromuscular junction, brain stem trauma or pleural space occupying lesions.

Peritoneal lavage to removed purulent septic material should exploratory celiotomy not be possible at that stage (by mean of local anaesthesia and a keyhole incision into abdomen through which a Foley’s catheter can be passed to lavage the abdomen).

Pain should be addressed. Patients will often remain unstable if left in severe pain.

Severely hypothermic patients must have this need appropriately addressed if they are to be stabilised.

How long should stabilisation take?

As fast as possible. Volume resuscitation in hypovolaemic shock should not take longer than 30-60 minutes.

This said the time required to stabilise a patient can be highly variable and will depend on the underlying condition. Some patients never reach sufficient stability to allow for interventions under anaesthetic. It must however be stressed that continuous and close monitoring of unstable patients is absolutely essential if life saving interventions that require a general anaesthetic are necessary. Only close and frequent monitoring will allow a well-timed decision as to when the best time to administer an anaesthetic might be.

It is important to remember that stabilisation should be achieved in the shortest safe period and once a patient is showing trends towards stabilisation urgent procedures under anaesthetic should be performed. In other words medical interventions may only provide a short window of opportunity during which more permanently stabilising procedures that require general anaesthesia (GA) can be applied. Delaying invasive interventions unnecessarily will cost a life in many situations.

Generally speaking stabilization should not take longer than a few hours. In most cases it should be achieved within the first hour or two after presentation.

Under what emergency situations can one not afford to wait before administering an anaesthetic?

If a patient needs such an urgent intervention to save its life (like an obstructed trachea in a dog that you cannot relieve without an anaesthetic such as a puff adder bite that needs an emergency tracheostomy or a trauma patient that will die without an immediate insertion of an ET tube or a bulldog with heat stroke that has such bad laryngeal oedema or collapse that it is cyanotic and deteriorating in front of your eyes).

If a patient is in life-threatening status epilepticus (such as with strychnine poisoning or following cranial trauma).

A dog or cat with a flail chest or pleural effusion that will not tolerate a conscious needle drainage or drain insertion under local anaesthetic for stabilisation.

A patient with rupture of an organ that is haemorrhaging causing haemothorax or haeomoperitoneum (such as a ruptured liver or spleen). These patients will require emergency transfusion whilst surgical intervention to stop the bleeding occurs.

A patient in a state of collapse following a neurotoxic snakebite that requires mechanical ventilation.

Patients with a ruptured gastro-intestinal tract, strangulation or volvulus lesion should undergo surgical correction as soon as possible. The longer contamination of the peritoneal cavity is present the poorer the outcome is.

When should primary intervention to correct the underlying problem be initiated?

Intervention to correct the underlying primary problem should be performed when the risk of delaying further treatment is greater than the benefit of continuing stabilisation. Complete normalisation may not yet have been achieved.

When further stabilisation is no longer possible due to ongoing deterioration of the patient’s condition.

When the patient is stable enough (i.e. not yet normalised) to undergo intervention to correct the primary problem.

As an example, a patient with septic peritonitis may benefit from surgical treatment before stabilisation to "normal" levels, as it is quite likely that this cannot be achieved before the abdomen has been lavaged.

Which emergency situations usually need stabilisation before anaesthetics can be administered?

Cats with obstructive uropathy that are hyperkalaemic. These cats should have their bladders needle drained and the hyperkalaemia should be resolved before catheterisation under general anaesthetic.

Dogs with GDV should be trocharised and urgently fluid loaded at the same time before an anaesthetic is given. Some of these patients can be stomach tubed by mouth without anaesthetic but most will require at least a short anaesthetic for this. If these dogs are in shock it is my/our opinion that the stomach should be deflated and the vascular compartment fluid and colloid loaded before surgical anaesthetic is administered.

All patients in shock as a result of trauma that is not resulting in immediate life threatening danger (such as listed above). Fight wounds and dogs involved in motor vehicle accidents are common examples. Adequate resuscitation is normally required before radiographic examinations, wound care or complete assessments can be made. It is important to remember however that a patient that has been injured may only destabilise after admission and as such trauma patients should be closely monitored.

Pyometra/septic peritonitis cases may need stabilisation although most cases are sufficiently stabile to intervene immediately. The general rule of thumb in any septic patient is to surgically drain or remove the source of sepsis without any or the minimum of delay. Any stabilisation without doing this can be expected to be short lived.

Cases that are clinically dehydrated should be rehydrated in the shortest possible time before urgent anaesthetics are administered.

Cases in low output cardiac failure that is not stable on treatment.

8. Anaesthesia

The appropriate use of anaesthetic agents is dependent on the clinical situation of the patient and a thorough knowledge of the clinical pharmacology of drugs used. There is little evidence to support the use of specific drugs and their influence on outcome is negligible. The most important determinate of outcome is the treatment and maintenance of stable cardiovascular and respiratory function (ensuring an adequate oxygen delivery to all cells in the body).

Essentially patients can be classified into three categories:

those who are stable may receive a standard induction or slightly reduced induction dose;

those who are unstable should have the anaesthetic slowly titrated to effect;

those who are moribund or near death where minimal anaesthesia should be used.

General principles to be remembered when anaesthetising compromised patients include the optimisation of tissue perfusion and oxygen delivery to all organ systems while achieving analgesia, muscle relaxation and unconsciousness.

A. Pre-anaesthetic Management

In certain cases prompt surgical treatment is life saving (uncontrolled haemorrhage, perforated intestines, ruptured pyometra or uterus, etc) but generally the accompanying shock is more dangerous than the initial trauma. In these cases the treatment of shock is the priority before surgical correction is attempted.

Oxygen supplementation

This is almost always indicated and can be achieved with a facemask, nasal catheter, endotracheal tube or oxygen chamber. The use of an oxygen chamber is not ideal, as it does not allow access to the patient. Oxygen supplementation is especially important in cases with respiratory and cardiac compromise. In anaemic patients correcting haematocrit is more important than oxygen therapy. Remember not to stress animals attempting to administer oxygen. Free flow oxygen passed the face may be the best way of administration in cases that are overly anxious.

Analgesics and sedatives and premedications

Useful premedications include morphine and diazepam and these are usually indicated. Acetylpromazine and alpha-2 agonists are generally contraindicated. These are required for the management of pain, fear and apprehension. Analgesia should be applied as soon as possible and be maintained post trauma or post-surgery.

Anticholinergics

These are not routinely used in trauma patients as they increase myocardial oxygen demand and reduce the threshold for arrhythmias. Atropine or glycopyrrolate may be used when vagal influence affect cardiac function or secretions need to be controlled. Trauma patients are often not starved and this increases the incidence of aspiration. Methods to reduce aspiration include position of the head lower than the abdomen, immediate intubation with a cuffed endotracheal tube and suctioning if reflux occurs.

B. Induction Agents

It is always best to remember that the drug with which you have the most personal experience is most likely to be the safest drug in your hands. Always remember that anaesthetic drugs administered to a patient in shock in the same way as they would be used in a healthy patient will aggravate shock. This is because these drugs have potent respiratory and cardiovascular depressive effects that will exacerbate the state of shock.

Intravenous agents:

Barbiturates are known to decrease myocardial contractility, depress baroreceptor reflexes, vasodilatation, decreases venous return and depress respiration. They are poor analgesics and have no muscle relaxation. Barbiturates are arrhythmogenic when given rapidly intravenously. Propofol has less of myocardial depressant effect and fewer arrhythmias than thiopentone. The degree of myocardial depression is a function of dose and rate of injection. Barbiturates are highly protein bound and the acid-base balance; albumin content and concurrent drug administration influence their pharmacokinetics. Critically ill patients are often acidotic and hypoproteinemic and thus require lower anaesthetic doses.

Propofol causes similar haemodynamic effects as thiopentone and cannot be recommended over thiopentone unless the patient is cardiovascularly stable.

Both these agents should be given very slowly intravenously to effect to achieve a plane of anaesthesia just sufficient for intubation. Rapid administration of these agents in states of myocardial hypoxia can be fatal and it is therefore essential to supplement oxygen and ensure adequate blood pressure before induction. Propofol has a greater tendency than thiopentone to cause induction apnoea, especially if given too fast. This may prove fatal in hypoxaemic animals.

Ketamine is one of the few drugs with indirect cardiovascular stimulatory properties. It raises blood pressure secondary to a sympathetic increase in heart rate and cardiac output. It is contraindicated in any patient with myocardial disease or in a patient in maximal sympathetic stimulation (which is often the case in severe trauma or haemorrhagic shock). Ketamine is a poor muscle relaxant and spontaneous movement is possible. Ketamine increases intracranial pressure and is contra-indicated in cranial trauma. Benzodiazepines may be used with ketamine to enhance muscle relaxation.

Opioid induction

This mode of induction is the preferred method for induction in compromised patients but needs to be used with caution and a complete description of the use of this modality is beyond the scope of this short review. Opioids are most commonly combined with benzodiazepines and the opioid drugs most commonly used include fentanyl, morphine and midazolam. Mixed agonist-antagonists include buprenorphine and are not preferred due to their ceiling effects and an inability to titrate the analgesia.

Because opioids (especially fentanyl) result in respiratory depression pre-oxygenation is advisable. Bradycardia may occur and is treatable with anticholinergics and in refractory cases adrenaline may be used. Morphine is associated with a dose dependent histamine release and may result in hypotension. Adequate fluid loading can minimise this negative effect and should not be a reason for withholding morphine administration. Opioid combinations (eg fentanyl and morphine) have been used successfully. Opioid induction (with for example diazepam and fentanyl) is slower than conventional methods and if rapid intubation is required it cannot be recommended. Opioids are administered to the point where tracheal intubation is possible.

Inhalation agents

These are as hypotensive as barbiturates and are only safer because the period of time from drug application to surgical anaesthesia is longer thus allowing for a longer period of time for the body to establish homeostasis for their depressant effects on blood pressure. Halothane and isoflurane both cause a dose dependent cardiovascular depression. Isoflurane is the least depressant at equipotent minimum alveolar concentration values. Isoflurane is also less arrhythmogenic and causes a quicker induction than halothane. If a traumatised patient is alert it is likely to struggle with gas induction. This struggle may result in increased circulating catecholamines which may result in arrhythmias (especially with halothane) as halothane sensitises the myocard to adrenaline. Inhalation agents have no muscle relaxing or analgesic properties.

Some dogs in severe shock require no anaesthesia and only some analgesia in order for surgery to be performed. A less depressant form of analgesia using a local anaesthetic block should be considered. Epidural anaesthesia can be useful tool for abdominal or hind limb procedures. Patients should be fluid loaded as epidural anaesthesia can result in vasodilatation. The lowest possible dose of anaesthetic should be used and all intravenous agents should be titrated to effect.

Maintenance of anaesthesia.

Some patients may require mechanical ventilation. The fact that a patient is breathing does not necessarily mean it is adequately ventilating. Remember also that an anaemic, pale patient may not show cyanosis. Close monitoring of the measures of blood pressure, perfusion and tissue oxygenation must be maintained constantly throughout the period of anaesthesia. In addition to close physical assessment of these measures of the patient’s condition, additional monitoring that is very useful includes ECG, pulse oximetery, blood pressure (invasive arterial and or central venous pressure), and capnography. Haemodynamic stability is maintained with fluids, ionotropic agents (dobutamine constant rate infusion), vasoconstrictors (dopamine or adrenalin constant rate infusion) and colloids. Direct arterial blood pressure measurement and central venous pressure can be used to monitor haemodynamic stability. Urinary output is easily monitored with a catheter and is an important indicator of renal perfusion and fluid balance.

A combination of inhalation agents, opioids, benzodiazepines or ketamine can be given for maintenance.

Hypothermia kills and patients should be warmed or the body temperature maintained using hot warm bottles, warm water blankets, heating lamps or warm air heating devices during all anaesthetic procedures and post operative care should pay special attention to this aspect.

Useful references include (but are not limited to) the following texts:

Manual of Canine and Feline Emergency and Critical Care

Ed: L King, R Hammond.

Published by BSAVA, United Kingdom

1999

ISBN 0 905214 40 4

Emergency Medicine in Small Animal Practice

The Compendium Collection

Published by Veterinary Learning Systems, Trenton, New Jersey.

1997

ISBN 1 884254 24 1

Small Animal Emergency and Critical Care. A Manual for the Veterinary Technologist.

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Anaesthesia: Monitoring

ANAESTHESIA

The following guideline should be followed for the monitoring of animals under anaesthesia: The monitoring, maintenance and recovery from anaesthesia should be effected by registered personnel and or trained non registered personnel under supervision of a registered veterinarian who must be on the premises. Surgery, monitoring and maintenance should not be done by the same person.

All animals should be monitored after surgery and not discharged unless adequately recovered from anaesthesia. All animals must be fully conscious and ambulatory before discharging them from an animal facility.

Should it be necessary for a practitioner to deviate from the aforementioned the owner should be advised of the risks involved.

(Published -December 1997)

Refer to the guideline document under Guidelines titled " Recommendations for Monitoring of Anaesthesia" below.

Anaesthesia: Starving Patients

The delay or postponement of appropriate treatment of an emergency or other condition which, if not given timeous attention, could result in unwanted complications and lead to a veterinarian being found guilty at an inquiry. Rule 4.1.2 of the Veterinary and Para-Veterinary Professions Act determines that a veterinarian is morally obliged to serve the public to the best of his/ her ability and in terms of the latest scientific knowledge. It is clear that there can be no grounds for defence on the basis of outdated information. One example is the delay of general anaesthesia for fear that complications may develop in an animal who has recently eaten.

A number of practitioners have disputed the relevance and practicality of scavenging of waste anaesthetic gas from operating theatres. In a recent survey of 161 practitioners in South Africa it came to light that only 11.8% of practitioners applied any form of scavenging to prevent contamination of the operating room environment. Volatile anaesthetic agents and some carrier gases may pose a significant health risk for staff. The welfare of animals, employees, and the clients are the concern of the veterinary profession and its governing institution.

The Occupational Health and Safety Act of RSA (Act 85 of 1993 as amended by Act 181 of 1993), requires that every employer instructs employees on the hazards to their health with regard to any substance they may use, handle, store or transport (Section 8, 9 and 12). As halothane or any of the other volatile anaesthetic agents are considered a potential health risk which is augmented by the fact that the European Union and the United Sates have established maximum exposure levels, we as employers are required to take the necessary precautions as described in Act 85 of 1993. The act requires that the employer instruct the employee on the appropriate methods to handle and use hazardous substances and it also states that an employer must take appropriate measures to prevent unnecessary exposure to any hazardous substance. Failure do so, is considered under the act to be an offence. Veterinarians are advised to take cognisance of this fact as litigation may result. The council by encouraging scavenging of anaesthetic agents wishes to protect veterinarians from potential legal consequences. The Occupational Health and Safety Act is administered by the Department of Labour.

Active scavenging devices are expensive and are not mandatory for veterinary facilities. Simple passive scavenging systems can be implemented as follows:

A pipe is connected to the pressure relief valve (pop-off valve) and another conduit through the outside wall of the room at a level below the height of the anaesthetic machine.

Installation of an activated charcoal container on the anaesthetic machine absorbs exhaled anaesthetic gasses. Companies specialising in this kind of equipment must install this. Like the soda-lime canister, the activated charcoal must be replaced from time to time. It is also a more costly system but convenient for mobile anaesthetic machines.

Alternative a plastic refuse bag (good quality) can also be attached to the pop-off valve and emptied outside after the procedure.

In cases where gas masks are used (like birds) anaesthetic gases escape into the room and there is an even greater potential for risk. In these cases it is recommended that a well-ventilated room be used, the masks fits a tightly as possible and if attached to breathing circuit scavenging is possible.

Acknowledgement

This article has been based on a previous publication by the author: Joubert KE 1999 The hidden dangers of the anaesthetic machine. Journal of the South African Veterinary Association: 70: 4: 140 – 141. Prof AM Lübbe is acknowledged for his input into the article. A list of references is available on request.

(Published - April 2003)

Admissions to Veterinary Clinical Facilities

HOSPITAL ADMISSIONS

What Council expects from a veterinarian when an animal is admitted to a facility for treatment and care.

The companion animal practitioner leaves his patients not fully recovered from surgery or the rural practitioner spays a dog at 7:00 and then leaves on farm calls.

It is expected of the veterinarian to ensure that the animal is monitored by an adequately trained person and that the veterinarian or his / her colleague attends to the patient at least once a day over and above the surgery performed on the animal.

Most practitioners leave their practices at 7:00 p.m. and patients are left on their own.

An animal should not be hospitalised over night at a clinic except if full-time supervision is available ( by an adequately trained person) at the clinic / hospital concerned.